Intensive lifestyle intervention consisted of sessions with a nutritionist and personal trainer, as well as group sessions for support and reinforcement. Target weight loss in the intensive lifestyle intervention group was at least 7% of initial body weight.

The usual care groups received diabetes support and education.

Principal Findings:

Overall, 5,145 patients were randomized. The mean age was 59 years, 59% were women, 14% had a history of cardiovascular disease, and mean body mass index was 36 kg/m2. The mean glycated hemoglobin was 7.2%, mean systolic blood pressure was 128 mm Hg, mean high-density lipoprotein cholesterol was 43 mg/dl, and mean low-density lipoprotein cholesterol was 112 mg/dl.

Average weight loss from baseline to 1 year was -8.6% in the intensive lifestyle intervention group versus -0.7% in the control group (p < 0.001).

The trial was terminated early at a median of 9.6 years of follow-up due to futility in showing a difference in adverse cardiovascular events. Mean follow-up was planned to 13.5 years.

The primary outcome, incidence of cardiovascular death, myocardial infarction, stroke, or hospitalization for angina, occurred at a rate of 1.8 events/100 person-years in the intervention group versus 1.9 events/100 person-years in the control group (p = 0.51).

The primary outcome (adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65–0.99; p = 0.039) and secondary outcome (adjusted HR 0.79, 95% CI 0.66–0.95; p = 0.011) were lower among those in the intensive lifestyle group who lost at least 10% of their bodyweight compared with the control group.

Interpretation:

Among overweight/obese patients with type 2 diabetes, intensive lifestyle intervention failed to reduce the incidence of adverse cardiovascular events. As a result, the trial was terminated early due to futility. Despite no benefit on the primary outcome, intensive lifestyle intervention resulted in significant weight loss and reduced the prevalence of cardiovascular risk factors; however, this benefit became somewhat attenuated between 1 and 4 years. The control group had modest improvements in cardiovascular risk factors and even had a lower low-density lipoprotein cholesterol level versus the intensive lifestyle intervention group, which might have contributed to the overall null trial findings.

The cardiovascular event rate during the study was lower than anticipated. This likely reflects good background therapy (e.g., antiplatelet agents, statins) among study participants. Also, diabetes is but one component of a patient’s overall risk for an adverse cardiovascular event.

References:

The Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol 2016;Aug 30:[Epub ahead of print].